[syunchow]

I'm trying to seperate my compound tert-butyl 3-hydroxy-4-methylenepiperidine-1-carboxylate from methyl phenyl sulfoxide using EtOAC:Pet. ether 1:4. Methyl phenyl sulfoxide was eluted first and quickly but my compound did not get eluted out at all. I can see a brown band on top of the silica column, tried to flush it out using pure ethyl acetate but did not work. Please help.

[syunchow]

and is there any way of recovering my compound ?

[discodermolide]

Your compound is a carboxylic acid, correct?
Why column it, do a simple base acid wash and you have it.
Now you suspend the silica with your compound in sodium hydroxide, stir and filter wash with toluene. Add fresh toluene and adjust the pH of the aqueous phase to 1 - 2 and extract the free acid into the toluene. Evaporate the solvent and you have it.
If toluene does not dissolve the compound use dichloromethane.
good luck

[syunchow]

Hi discodermolide,
Thanks for your suggestion. It is not a carboxylic acid (the carboxylate comes from the boc protecting group) - my compound has a hydroxyl group. Still trying to figure out what's happened since this is a literature protocol

[discodermolide]

Hi discodermolide,
Thanks for your suggestion. It is not a carboxylic acid (the carboxylate comes from the boc protecting group) - my compound has a hydroxyl group. Still trying to figure out what's happened since this is a literature protocol

So it is a carbamic acid t-butyl ester. Change your solvent to methylene chloride containing 1-5%methanol and you.should move it off the column.
Next time try several TLC systems to get an idea of how it elites before doing the column, 
Good luck

[Doc Oc]

Next time try several TLC systems to get an idea of how it elites before doing the column

This.  You should never run a column without doing TLCs yourself, even if you're following a literature procedure for the same compound.

[syunchow]

I have done a TLC before I run the column! My compound has a nice Rf value of 0.43 - unfortunately it just didnt translate into column separation.

[orgopete]

I have done a TLC before I run the column! My compound has a nice Rf value of 0.43 - unfortunately it just didnt translate into column separation.

That is unusual. Usually one would cut back on the polarity of the eluent if your compound had an Rf that high. So, just using your TLC solvent should have eluted your compound in a few column volumes.

[syunchow]

I have a brief talk with one of the senior chemists in my group - apparently compound with hydroxyl group (i.e serine-containing peptide) tends to stick on the column in EtOAc eluting system? Any idea why?

p.s I will be extra careful next time and test other solvent systems before running column

[Dan]

I have done a TLC before I run the column! My compound has a nice Rf value of 0.43 - unfortunately it just didnt translate into column separation.

Did you do this immediately before loading the crude onto the column or were there work up procedures between running the TLC and running the column? If there were stages between TLC and column it is possible that your compound was degraded/destroyed/washed out in these procedures. I have also observed quite striking shifts in R_F after workup procedures as well, for example it is quite common in borohydride reductions in my experience - where presumably boron complexes are hydrolysed on workup, changing the R_F.

Make sure you have a TLC of exactly the material that you are loading onto the column.

You could also run a 2D TLC to check for decomposition on silica.

[manishbiyani]

syunchow:

Please make sure that you don't throw the silica gel which you think contains your compound.
a) Your compound is very polar
b) The system pet ether/ EA won't be good enough to pull out your compound
c) Try to use dcm: methanol start from 95:5 to 9:1, if still it doesnt come then increase to 8.5:1.5
d) Did you check the NMR of the crude mixture (whether it contained desired product.

Hope this suggestion helps.

[manishbiyani]

Syunchow:

I forgot to mention...these are all other possibilities if you have already taken into consideration the points related to TLC system by other members (i.e. Rf before column, 2D etc)

[Dan]

If it really is a polarity problem, which I personally doubt, you can use what we call WIPE-127. This is 1:2:7 water/isopropanol/ethyl acetate, you can column free sugars with it (the isopropanol/ethyl acetate ratio can be varied, but do not exceed 10% water), and they are far more polar than the compound in question.

[syunchow]

Thanks everyone for your advice
I've managed to fix the problem - it seems that there's major streaking when I used EtOAC/Pet. ether system (from the -OH group?). I used 100% DCM to 5% MeOH in DCM and that, works beautifully - most of my compound was recovered! YAY!!!!!!!